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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
N6-methyladenosine promotes osteogenic differentiation of PDLSCs from periodontitis patients
Xiaochen Zhang1, Jia Liu1, Jie Gao1
1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Objectives:
This study aimed to investigate the mechanism of N6-methyladenosine (m6A) in the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) from periodontitis patients.
Methods:
Differentially m6A-methylated lncRNA/mRNA profiles were detected by a m6A epitranscriptomic microarray. Bioinformatics analysis was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The transfection efficiency of the lentivirus was detected. The osteogenic activity of PDLSCs from periodontitis patients (PPDLSCs) was assessed.
Results:
The microarray results showed that 275 lncRNAs and 1292 mRNAs were significantly differentially methylated between PPDLSCs and PDLSCs from healthy people. Among those lncRNAs, lncRNA4114 (transcript_ID: ENST00000444114) showed both reduced m6A methylation levels and expression levels in PPDLSCs. Further bioinformatics analysis predicted that the differentially methylated mRNAs were mainly involved in cell interaction, stem cell pluripotency, and osteogenic differentiation signals. Then, overexpression of methyltransferase like 3 (METTL3) promoted the osteogenic differentiation of PPDLSCs, while knocking down METTL3 showed an inhibitory effect. Furthermore, METTL3 overexpression promotes the stability of lncRNA4114 to upregulate the expression level. Moreover, lncRNA4114 overexpression promoted the osteogenic differentiation of PPDLSCs.
Conclusion:
METTL3 promotes the osteogenic differentiation of PPDLSCs by regulating the stability of lncRNA4114.

